A vaccine regimen utilizing adenovirus (Ad)-HIV or -SIV recombinant priming and protein boosting has shown promise in animal models. Humoral, cellular, and mucosal immune responses were elicited, and long-lasting protection was observed in chimpanzees against a heterologous, primary, non-syncytial-inducing (NSI) HIV isolate, the type transmitted among people. Decreased viral burdens during acute infection were also demonstrated in immunized rhesus macaques after mucosal challenge with a virulent, pathogenic SIV strain. These studies have stimulated testing of the Ad-recombinants in human phase I trials. Continued pre-clinical studies have contributed to future AIDS vaccine design. Non-MHC-restricted CD8+ T-cell antiviral activity was shown to complement broadly reactive antibody with neutralizing activity in completely protecting a chimpanzee from an NSI, HIV-1 challenge. Multiple factors, including neutralizing antibody and viral-specific CTL responses appeared responsible for slow disease progression observed in mucosally challenged rhesus macaques. Mucosal antibody responses did not, however, appear to modulate disease outcome in chronically infected animals. Immunization with a peptide polymer representative of the CD4 binding site region on the viral envelope was evaluated after priming with Ad-SIV env and appeared to enhance viral infection and disease progression. Whether this effect was immune- or antigen-based is under study. The results will have important implications for future vaccine designs targeted to CD4, the primary HIV receptor. Using attenuated poxvirus (NYVAC) recombinants and protein boosts, we confirmed that immunization with HIV-1 confers cross-protection against HIV-2 challenge, although reciprocal cross- protection was not observed. Identification of cross-protective epitopes could provide the basis for globally effective vaccines. A NYVAC-SIV recombinant prime/boost strategy elicited elevated levels of CD8+ antiviral activity which contributed to reductions in viral burdens post challenge and a slower disease course. The ability to elicit higher levels of this innate activity should contribute to overall vaccine protective efficacy.AIDS title: Adenovirus and Attenuated Poxvirus Recombinants and Subunit Boosting in AIDS Vaccine Development. - adenovirus vectors, AIDS, HIV, humporal immunity, Pox virus vectors, SIV, vaccine, Animal models, cell-mediated immunity, mucosal immunity, - Human Tissues, Fluids, Cells, etc.